The broad objective of this research work is to simplify procedures for development of the animal model system for an in-vivo study of the microcirculation in sickle cell anemia. This will be accomplished by transfusion of rats with human sickle blood. The vascular and intravascular sequence of events associated with the sickling transformation and resulting microvascular occlusion will be studied by direct microscopy, first in mesentery, and then extend to pial and cremasteric microvascular beds. The observation will be paralleled by similar studies with isolated rat mesoappendix preparation perfused with human blood. Histological examination of a variety of tissues will also be made. Specifically, the relationship of the sickling to pattern of blood flow will be investigated. This will include an examination of changes in flow velocity, cell aggregation, flow reversal, shunting, sludging, stasis, vessel obstruction, and level of vasomotor tone and reactivity to selected vasoactive agents. An examination will be made of a variety of factors which may promote or inhibit vascular obstructions due to sickling. These factors will include anoxia, acidosis, fluid and electrolyte inbalance, injury, shock, the effects of anesthesia, blood transfusion, i.v. hydration, and a range of selected therapeutic measures.